PROJECT SUMMARY/ABSTRACT African Americans face a two-fold higher risk of ischemic stroke than white residents of the U.S. The reasons for this black-white stroke disparity are not completely known. This proposal seeks to identify whether atrial cardiopathy, a novel risk factor, partly explains the higher stroke risk in blacks. Compared to whites, blacks experience less atrial fibrillation, a heart-rhythm disorder that is one of the strongest known risk factors for stroke. In the prevailing clinical paradigm, it is thought that atrial fibrillation is required for blood clots to form in the heart's left atrium, from where they can embolize to the brain and cause stroke. However, recent research indicates that embolization from the left atrium can occur when there are abnormalities in atrial tissue and function?a condition referred to as atrial cardiopathy?regardless of whether there is atrial fibrillation. Preliminary data suggest that atrial cardiopathy manifests differently in blacks than whites: more often with left atrial abnormality on a 12-lead electrocardiogram (ECG) and less often with atrial fibrillation or its typical accompaniment, left atrial enlargement on an echocardiogram. As a result, atrial thromboembolism may often go unrecognized in blacks because it occurs in the absence of atrial fibrillation and atrial enlargement. The proposed research will test the central hypothesis that currently unexplained disparities in stroke between whites and blacks can be partly explained by differences in the manifestation of atrial cardiopathy. This application is for an ancillary study to the REasons for Geographic and Racial Differences in Stroke (REGARDS) study and the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS). REGARDS is a longitudinal cohort study that seeks to shed light on the relationship between baseline risk factors and future stroke in >30,000 black and white individuals. GCNKSS is a population-based epidemiological study of racial disparities in the incidence and outcomes of stroke in a biracial population of 1.3 million. Taking advantage of the complementary designs of these studies, the proposed research will first determine the relationship between baseline ECG-defined left atrial abnormality, race, and future stroke in REGARDS. It will then determine black-white differences in GCNKSS in markers that signify a potential atrial thromboembolic cause of stroke. Specific Aim 1 will test the hypotheses that blacks have a higher prevalence of left atrial abnormality, that left atrial abnormality is associated with future stroke, and that left atrial abnormality contributes to the higher stroke risk in blacks. Specific Aim 2 will test the hypotheses that black patients with ischemic stroke more often have ECG-defined left atrial abnormality and less often have echocardiographic left atrial enlargement than whites. All ECGs and a subset of echocardiogram images will be centrally interpreted. This research promises to show that blacks' higher stroke risk partly reflects actionable differences in the biology of stroke. Such findings may ultimately lead to therapy using existing medications approved for atrial fibrillation.